International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701

_________________________________________________________________________Review Paper

Microspheres - An Overview

Prasanth v.v 1, Akash Chakraborthy Moy2, Sam T Mathew3, Rinku Mathapan4

1. Department of Pharmaceutics, Gautam College of Pharmacy, Bangalore, India.

2. Research Scholar, Department of Pharmaceutics, Gautam College of Pharmacy,
Sultanpalya, Bangalore, India.
3. Accenture Pharmaceutical services, Bangalore, India.
4. Department of Pharmacognosy, Gautam College of Pharmacy, Bangalore,India.
___________________________________________________________________________________________
Abstract
There are various departments of medicine like cancer, pulmonary, cardiology, radiology, gynaecology, and
oncology etc, numerous drugs are used and they are delivered by various types of drug delivery system.
Among them microspheric drug delivery system has gained enormous attention due to its wide range of
application as it covers targeting the drug to particular site to imaging and helping the diagnostic features. It
also has advantage over various other dosage forms like we know for lungs disease now a days aerolised drugs
are used for local delivery of drugs but it has disadvantage of shorter duration of action so for sustained
release and reducing side effects and hence to achieve better patient compliance microspheres can be used. It
also has advantage over liposomes as it is physicochemically more stable. Moreover the microspheres are of
micron size so they can easily fit into various capillary beds which are also having micron size. The purpose of
the review is to compile various types of microspheres, different methods to preparation, its applications and
also various parameters to evaluate their efficiency.
Key words: microspheres, charecterisation of microspheres, drug delivery

INTRODUCTION

In contrast to drug delivery system, the word throughout the matrix either as a molecular
novel is searching something out of necessity. The dispersion of particles” (or) can be defined as
drug has to be delivered for a prolonged period of structure made up of continuous phase of one or
time and many medicines have to be taken more miscible polymers in which drug particles are
simultaneously in case of chronic patients. dispersed at the molecular or macroscopic level.4 It
Frequent administration of drug is necessary when has a particle size of (1-1000nm).3 Further,
those have shorter half life and all these leads to currently available slow release oral dosage forms,
decrease in patient’s compliance.1 In order to such as enteric coated/ double-layer tablets which
overcome the above problems, various types of release the drug for 12-24 hours still result in
controlled release dosage forms are formulated and inefficient systemic delivery of the drug and
altered, so that patient compliance increase through potential gastrointestinal irritation.
prolonged effect , adverse effect decreases by Microencapsulation for oral use has been employed
lowering peak plasma concentration.2 The to sustain the drug release, and to reduce or
controlled release dosage form maintaining eliminate gastrointestinal tract irritation. In
relatively constant drug level in the plasma by addition, multiparticulate delivery systems spread
releasing the drug at a predetermined rate for an out more uniformly in the gastrointestinal tract.
extended period of time. One such in Microspheres This results in more reproducible drug absorption
as carriers of drug become an approach of and reduces local irritation when compared to
controlled release dosage form in novel drug single-unit dosage forms such as no disintegrating,
delivery system.2 Microspheres are defined as polymeric matrix tablets. Unwanted intestinal
“Monolithic sphere or therapeutic agent distributed retention of the polymeric material, which may
_______________________________________ occur with matrix tablets on chronic dosing, can
*Address for correspondence: also be avoided.4 Microencapsulation is used to
E-mail: [email protected] modify and retard drug release. Due to its small
particle size, are widely distributed throughout the

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 International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701

gastrointestinal tract which improves drug normal surrounding tissues.9It differs from drug
absorption and reduces side effects due to localized delivery system, as radio activity is not released
build-up of irritating drugs against the from microspheres but acts from within a
gastrointestinal mucosa.5 radioisotope typical distance and the different kinds
of radioactive microsphers are α emitters, β
TYPES OF MICROSPHERES emitters, γ emitters.10

Bioadhesive microspheres Polymeric microspheres

Adhesion can be defined as sticking of drug to The diffent types of polymeric microspheres
the membrane by using the sticking property of the can be classified as followsand they are
water soluble polymers. Adhesion of drug delivery biodegradable polymeric microspheres and
device to the mucosal membrane such as buccal, Synthetic polymeric microspheres.
ocular, rectal, nasal etc can be termed as bio
adhesion. These kinds of microspheres exhibit a Biodegradable polymeric microspheres
prolonged residence time at the site of application Natural polymers such as starch are used with
and causes intimate contact with the absorption site the concept that they are biodegradable,
and produces better therapeutic action.6The effect biocompatible, and also bio adhesive in nature.
of different polymers on bio adhesive microspheres Biodegradable polymers prolongs the residence
are given in table I. time when contact with mucous membrane due to
it’s high degree of swelling property with aqueous
Magnetic microspheres medium , results gel formation. The rate and extent
This kind of delivery system is very much of drug release is controlled by concentration of
important which localises the drug to the disease polymer10 and the release pattern in a sustained
site. In this larger amount of freely circulating drug manner. The main drawback is, in clinical use drug
can be replaced by smaller amount of magnetically loading efficiency of biodegradable microspheres is
targeted drug. Magnetic carriers receive magnetic complex and is difficult to control the drug release.
responses to a magnetic field from incorporated However they provide wide range of application in
materials that are used for magnetic microspheres microsphere based treatement.11
are chitosan, dextran etc.5 The different type are
Therapeutic magnetic microspheres: Are used Synthetic polymeric microspheres
to deliver chemotherapeutic agent to liver tumour. The interest of synthetic polymeric
Drugs like proteins and peptides can also be microspheres are widely used in clinical
targeted through this system.6 application, moreover that also used as bulking
Diagnostic microspheres: Can be used for agent, fillers, embolic particles, drug delivery
imaging liver metastases and also can be used to vehicles etc and proved to be safe and
distinguish bowel loops from other abdominal biocompatible.11But the main disadvantage of these
structures by forming nano size particles kind of microspheres, are tend to migrate away
supramagnetic iron oxides.7 from injection site and lead to potential risk,
embolismand further organ damage. 12 Different
Floating microspheres kinds of polymers used for microspheres are given
In floating types the bulk density is less than the in table II.
gastric fluid and so remains buoyant in stomach
without affecting gastric emptying rate. The drug is METHOD OF PREPERATION
released slowly at the desired rate, if the system is
floating on gasteric contentand increases gastric Incorporation of solid, liquid or gases into one
residence and increases fluctuation in plasma or more polymeric coatings can be done by micro
concentration. Moreover it also reduces chances of encapsulation technique.1 The different methods
striking and dose dumping. One another way it used for various microspheres preparation depends
produces prolonged therapeutic effect and therefore on particle size, route of administration, duration of
reduces dosing frequencies. Drug (ketoprofen) drug release and these above characters related to
given through this form.8 rpm, method of cross linking, drug of cross linking,
evaporation time, co-precipitation etc.5 The various
Radioactive microspheres methods of preparations are
Radio emobilisation therapy microspheres sized
10-30 nm are of larger than capillaries and gets Emulsion solvent evaporation technique
tapped in first capillary bed when they come In this technique the drug is dissolved in
across. They are injected to the arteries that lead to polymer which was previously dissolved in
tumour of interest. So all these conditions chloroform and the resulting solution is added to
radcioactive microspheres deliver high radiation aqueous phase containing 0 .2 % sodium of pvp as
dose to the targeted areas without damaging the emulsifying agent. The above mixture was agitated

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at 500 rpm then the drug and polymer (eudragit) but may loose crystalinity due to fast drying
was transformed into fine droplet which solidified process.4
into rigid microspheres by solvent evaporation and
then collected by filtration and washed with Emulsion-solvent diffusion technique
demineralised water and desiccated at room In order to improve the residence time in colon
temperature for 24 hrs.12 Aceclofenac microspheres floating microperticles of ketoprofen were prepared
were prepared by this technique. using emulsion solvent diffusion technique. The
drug polymer mixture was dissolved in a mixture
Emulsion cross linking method of ethanol and dichloromethane (1:1) and then the
In this method drug was dissolved in aqueous mixture was added dropwise to sodium lauryl
gelatine solution which was previously heated for 1 sulphate (SLS) solution. The solution was stirred
hr at 40 0C. The solution was added drop wise to with propeller type agitator at room temperature at
liquid paraffin while stirring the mixture at 1500 150 rpm for 1 hr. Thus the formed floating
rpm for 10 min at 35 oC, results in w/o emulsion microspheres were washed and dried in a dessicator
then further stirring is done for 10 min at 15 0C. at room temperature. The following microperticles
Thus the produced microspheres were washed were sieved and collected.4
respectively three times with acetone and isopropyl
alcohol which then air dried and dispersed in 5mL Multiple emulsion method
of aqueous glutaraldehyde saturated toluene Oral controlled release drug delivery of
solution at room temperature for 3 hrs for cross indomethacin was prepared by this technique. In
linking and then was treated with 100mL of 10mm the beginning powder drug was dispersed in
glyciene solution containing 0.1%w/v of tween 80 solution (methyl cellulose) followed by
at 37 0 C for 10 min to block unreacted emulsification in ethyl cellulose solution in ethyl
glutaraldehyde.18 Examples for this technique is acctate. The the primary emulsion was then re
Gelatin A microspheres. emulsified in aqueous medium. Under optimised
condition discrete microspheres were formed
Co-acervation method during this phase.4
Co-acervation thermal change: Performed by
weighed amount of ethyl cellulose was dissolved in Ionic gelation
cyclohexane with vigorous stirring at 80 0C by Alginate/chitosan particulate system for
heating. Then the drug was finely pulverised and diclofenac sodium release was prepared using this
added with vigorous stirring on the above solution technique. 25 % (w/v) of diclofenac sodium was
and phase separation was done by reducing added to 1.2 % (w/v) aqueous solution of sodium
temperature and using ice bath. Then above alginate. In order to get the complete solution
product was washed twicely with cyclohexaneand stirring is continued and after that it was added
air dried then passed through sieve (sieve no. 40) to dropwise to a solution containing Ca2+ /Al3+ and
obtain individual microcapsule.1 chitosan solution in acetic acid. Microspheres
Co-acervation non solvent addition: Developed which were formed were kept in original solution
by weighed amount of ethyl cellulose was for 24 hr for internal gellification followed by
dissolved in toluene containing propylisobutylene filteration for separation. The complete release was
in closed beaker with magnetic stirring for 6 hr at obtained at pH 6.4-7.2 but the drug did not release
500 rpm and the drug is dispersed in it and stirring in acidic pH.4
is continued for 15 mins. Then phase separation is
done by petroleum benzoin 5 times with continious Hydroxyl appetite (HAP) microspheres in
stirring.1After that the microcapsules were washed sphere morphology
with n-hexane and air dried for 2 hr and then in This was used to prepare microspheres with
oven at 50oc for 4 hr.1 peculiar spheres in sphere morphology
microspheres were prepared by o/w emulsion
Spray drying technique followed by solvent evaporation. At first o/w
This was used to prepare polymeric blended emulsion was prepared by dispersing the organic
microsphere loaded with ketoprofen drug. It phase (Diclofenac sodium containing 5% w/w of
involves dispersing the core material into liquefied EVA and appropriate amount of HAP) in aqueous
coating material and then spraying the mixture in phase of surfactant. The organic phase was
the environment for solidification of coating dispersed in the form of tiny droplets which were
followed by rapid evaporation of solvent.4 Organic surrounded by surfactant molecules this prevented
solution of poly (epsilon-caprolactone) (PCL) and the droplets from co solvencing and helped them to
cellulose acetate butyrate (CAB), in different stay individual droplets .While stirring the DCM
weight ratios and ketoprofen were prepared and was slowly evaporated and the droplets solidify
sprayed in different experimental condition individual to become microspheres.19
achieving drug loaded microspheres. This is rapid

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CHARECTERIZATION/ EVALUATION OF Thermal analysis of microcapsule and its

MICROSPHERES component can be done by using-
Differential scanning calorimetry (DSC)
Particle size analyser Thermo gravimetric analysis (TGA)
Microsphere (50 mg) was suspended in distilled Differential thermometric analysis (DTA)
water (5mL) containing 2%w/v of tween 80, To Accurately the sample was weighed and heated on
prevent microsphere aggregation, the above alumina pan at constant rate of 10oc/min under
suspension is sonicated in water bath and the nitrogen flow of 40 ml/min.1
particle size was expressed as volume mean
diameter in micrometer.20 UV-FTTR (Fourier transform infra red)
The drug polymer interaction and also
Optical microscopy degredation of drug while processing for
This method was used to determine particle size microencapsulation can be determined by FTIR.24
by using optical microscope (Meizer OPTIK) The
measurement was done under 450x (10x eye piece Stability studies
and 45x objective) and100 particles were By placing the microspheres in screw capped
calculated.21 glass container and stored them at following
conditions:
Scanning electron microscopy (SEM) 1. Ambient humid condition
Surface morphology was determined by the 2. Room temperature (27+/-2 0C)
method SEM. In this microcapsule were mounted 3. Oven temperature (40+/-2 0C)
directly on the SEM sample slub with the help of 4. Refrigerator (5 0C -80C).
double sided sticking tape and coated with gold It was carried out of a 60 days and the drug
film under reduced pressure.22 content of the microsphere was analysed.15

Swelling index
This technique was used for Characterization of Zeta potential
sodium alginate microspheres were performed with The polyelectrolyte shell was prepared by
swelling index technique Different solution incorporating chitosan of different molecular
(100mL) were taken such as (distilled water, buffer weight into the W2 phase and the resulting
solution of pH(1.2, 4.5, 7.4) were taken and particles were determined by zeta potential
alginate microspheres (100mg) were placed in a measurement.25
wire basket and kept on the above solution and
swelling was allowed at 37 o C and changes in APPLICATION OF MICROSPHERES
weight variation between initial weight of
microspheres and weight due to swelling was Medical application9
measured by taking weight periodically and  Release of proteins, hormones and peptides over
soaking with filter paper.23 extended period of time.
 Gene therapy with DNA plasmids and also
Entrapment efficiency delivery of insulin.
Microspheres containing of drug (5mg) were  Vaccine delivery for treatment of diseases like
crushed and then dissolved in distilled water with hepatitis, influenza, pertusis, ricin toxoid,
the help of ultrasonic stirrer for 3 hr, and was diphtheria, birth control.
filtered then assayed by uv-vis spectroscopy.  Passive targeting of leaky tumour vessels, active
Entrapment efficiency is equal to ratio of actual targeting of tumour cells, antigens, by intra-
drug content to theoretical drug content.23 arterial/ intravenous application.
 Tumour targeting with doxorubicin and also
X-ray diffraction treatments of leishmaniasis.
Change in crystalinity of drug can be  Magnetic microspheres can be used for stem
determined by this technique. Microperticles and cell extraction and bone marrow purging.
its individual components were analysed by the
 Used in isolation of antibodies, cell separation,
help of D & discover (Bruker, Germony).Scanning and toxin extraction by affinity
range angle between 8 0C - 70 0C.
chromatography.
Scan speed - 4o/min
 Used for various diagnostic tests for infectious
Scintillation detector
diseases like bacterial, viral, and fungal.
Primary silt=1mm
Radioactive microsphere’s application7
Secondary silt=0.6 mm.1
 Can be used for radioembolisation of liver and
spleen tumours.
Thermal analysis
 Used for radiosynvectomy of arthiritis joint,
local radiotherapy, interactivity treatement.

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 Imaging of liver, spleen, bone marrow, lung etc platform is used to detect six single nucleotide
and even imaging of thrombus in deep vein polymorphism, yittrium-90 microspheres is used to
thrombosis can be done. prevent tumour after liver transplantation and it’s
advanced way in delivery of vaccines and proteins.
Other applications
 Fluorescent microspheres can be used for CONCLUSION
membrane based technologies for flow It has been observed that microspheres are
cytomettry, cell biology, microbiology, better choice of drug delivery system than many
Fluorescent Linked Immuno-Sorbent Assay.7 other types of drug delivery system because it is
 Yttrium 90 can be used for primary treatment of having the advantage of target specificity and better
hepatocellular carcinoma and also used for pre- patient compliance. Its applications are enormous
transplant management of HCC with promising as they are not only used for delivering drugs but
results.26 also for imaging tumours, detecting biomolecular
interaction etc. So in future microspheres will have
FUTURE CHALLENGES an important role to play in the advancement of
medicinal field.
Future challenges of microspheres look bright
particularly in the area of medicinal field because
of its wide spectrum of application in molecular
biology, eg: microsphere based genotyping

Table I: Effect of polymers on bioadhesive microspheres21, 6, 18, 12

DRUG ROUTEOF BIOADHESIVE POLYMERS USE APPLICATION OF POLYMERS

ADMINISTRATION
Clonazepam Nasal Gelatin-Chitosan Higher concentration of drug is achieved in
brain.
Gentamicin Nasal DSM+LPC Combination of these polymers improves
nasal absorption.

Insulin Nasal DSM+LPC Helps to deliver insulin via nasal route.

Human growth Nasal DSM+LPC Improves absorption.

Hormone (hGH)
Propanalol Hcl Nasal Chitosan- Gelatin Controlled blood level profile as well as
increased bioavailability of drug.

Aceclofenac GI Eudragit (S100,RL100,RS100) Controlled release of drug is achieved.

Furosemide GI AD-MMS (PGEFs) Bioavailability Increases Higher AUC and

thereby absorption also increases.

Amoxicillin GI Ethylcellulose-Carbopol- 934P Therapeutic efficacy of drug increases

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Table II: Various types of polymers and their applicatio9, 14, 24, 25

POLYMER MECHANISM

Slower release of drug.

Modified starch, HPMC,Carbopol 974P

Ethyl Cellulose
Controlled release for longer period of time.

PLGA, Chitosan Vaccine delivery.

PLA, PLGA, Starchcyanoacrylate etc(PEG-) liposomes. Drug delivery without toxic side effects.

Magnetic polystyrene microspheres Specific cell labelling.

Affinity chromatography.
Polymer resins such as Agarosepolyacroline, sephadex

Chitosan coated PlGA microspheres Targeted drug delivery

Polyvinyl alcohol, polyacrylamide

Adsorption of harmful substances in blood.

Table III: list of drugs and vaccines which are given as microspheres

DRUG REASON FORMULATION

Chlorpromazine Microcapsule
(Anti psychotic).13 Long term administration has side effects and extra pyramidal effects and so low dose
would overcome both this disadvantage in microcapsule form the occurrence
Of degree of catatonia reduces &hence better therapeutic profile can be achieved.

Glipizide(anti- It has short biological half life of 3.4+/- 0.7hr and is rapidly eliminated because of its Microspheres
diabetic).14 short half life and chronic use attempts are made to control release parental in the form
of microspheres.

Salbutamol
sulfate(β2- It has short biological half life i.e. 4-6 hr. In case of drugs having short half life. Lot of Microencapsulation
bronchodilator).1 medicines has to be taken simultaneously for longer period of time so to overcome this
problem microencapsulation has been done which is capable of releasing the drug
gradually.

Pentoxifylline
(xanthine It has short half live and low bioavailability so to overcome the above problems Microspheres
derrivative).15 microspheres were prepared for pre oral administration.

Vaccines.16 1. Microspheres can deliver the antigen to the targeted site at the predetermined rate Microspheres
and duration so optimum response can be achieved.
2. The carrier will also prevent degradation of vaccines.
3.It reduces systemic side effects

Tramadol
.Hcl(synthetic Half life of the drug is 5 hr and the usual dose is 50-100mg every 4-6 hr with Microsphere
opoid).17 maximum dosage of 400mg/day.when given in the form of immediate release
formulation adverse effect like headache, nausea, were more which decreased when
given in the form of sustained release formulation and hence patient compliance
increased, as frequency of dosing decreased and this was achieved by microsphere
formulation.

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REFERENCES
Journal of pharmaceutical Sciences. 1997;
1. Ghulam M., Mahmood A., Naveed A., Fatima 59(2):68-74.
R.A., Comparative study of various 14.Chowdary K.P.R., Koteshwara R.N., Malathi
microencapsulation techniques. Effect of K.., Ethyl Cellulose Microspheres of Glipizide:
polymer viscosity on microcapsule Charecterization, InVitro and In Vivo
charecterestics, Pak.J.Sci.2009; 22 (3):291-300. Evaluation, Indian Journal of pharmaceutical
2. Mathew Sam T., Devi Gayathri S., Prasanth V. Sciences. 2004; 66(4): 412- 416.
V., Vinod B., Suitability of factorial design in 15.Tamizharsi S., Rathi C.J., Rathi., Formulation
determining the processing factors affecting and Evaluation of Pentoxyfylline-Loaded Poly
entrapment efficiency of albumin microspheres, (ε-caprolactone) Microspheres, Indian Journal
Journal of Pharmacy Research.2010; 3(5):1172- of pharmaceutical Sciences. 2008; 70(3):333-
1177. 337.
3. Karmakar U., Faysal M.M., Diclofenac as 16.Saravana K.A., Ramaswamy N.M., Chitosan
microspheres, The Internet Journal of Third Microspheres as Potential Vaccine Delivery
World Medicine. 2009; 8(1) Systems, International Journal of Drug
4. Mathew Sam T., Devi Gayathri S., Prasanth Delivery. 2010; 3(1):43-50.
V.V., Vinod B; NSAIDs as microspheres, The 17.Jeevana B., Sunitha J.G., Development and
Internet Journal of Pharmacology .2008;6(1). Evaluation of Gelatin Microspheres of
5. Li, S.P., Kowalski C.R., Feld K.M., Grim Tramadolhydrochloride, Journal of Young
W.M., Recent Advances in Microencapsulation Pharmacists.2009;1 (1):24-27.
Technology and Equipment, Drug Dev Ind 18.Dandagi MP., Masthiolimath S.V., Gadad P.A.,
Pharm.1988; 14: 353-376. Iliger R.S., Mucoadhesive Microspheres of
6. www.pharmainfo.net/reviews/bioadhesive- Propanalol Hcl for Nasal Delivery, Indian
microspheres-review, 24th Nov 2010 Patel JK, Journal of pharmaceutical Sciences. 2007;69
Patel RP, Amin AF, Patel MM, 4(6), (3):402-407.
12/16/2006. 19.Pradesh T.S., Sunny C.M., Varma K.H.,
7. Shanthi N.C., Dr.Gupta R., Mahato K.A., Ramesh P., Preperationn of microstuctured
Traditional and Emerging Applications of hydroxyapatite microspheres using oil in water
Microspheres: A Review, International Journal emulsion, Bull Matter.Sci. 2005; 28(5):383-
of Pharm Tech Research. 2010; 2(1):675-681. 390.
8. Najmuddin M., Ahmed A., Shelar S., Patel V., 20.Kannan.K., Karar.K.P., Manavalan.R.,
Khan T., Floating Microspheres Of Ketoprofen Formulation and Evaluation of Sustained
:Formulation and Evaluation, International Release Microspheres of Acetazolamide by
Journal Of Pharmacy and Pharmaceutical Solvent Evaporation Technique, J.Pharm.Sci &
sciences. 2010; 2(Suppl2):83-87. Res. 2009; 1 (1):36-39.
9. http://www.springerlink.com 21.Shaji J., Poddar A., Iyer S., Brain-Targeted
/content/r883r91q17576vx6/, 25th Nov 2010, Nasal Clonazepam Microspheres, Indian
DOI: 10.1007/0-306-46891-3_9, Hafeli U, Journal of pharmaceutical Sciences. 2009;
2002, Physics and Chemistry Basic of 71(6): 715–718.
Biotechnology. Focus on biotechnology. 22.Chowdary K.P.R., Suri B.J., Permeability of
Review. Radioactive Microspheres for Medical Ethylene Vinyl Accetate Copolymer
Application, 7:213-248. Microcapsules: Effect of Solvents, Indian
10.Yadav AV., Mote HH., Development of Journal of pharmaceutical Sciences. 2003;
Biodegradable Starch Microspheres for 65(1):62-66.
Intranasal Delivery, Indian Journal of 23.Soni L.M., Kumar M., Namdeo P.K., Sodium
pharmaceutical Sciences. 2008; 70 (2):170-174. alginate Microspheres for extending drug
11.Saralidze K., Leo H., Koole., Menno L., release: formulation and in vitro evaluation,
Knetsch W., Polymeric Microspheres for International Journal of Drug Delivery. 2010;
Medical Applications, Materials. 2010; 3:3357- 2(1):64-68.
3564. 24.Surini S., Anggriani V., Anwar E., Study of
12.Trivedi P., Verma A.M.L., Garud N., Mucoadhesive Microspheres Based on
Preperation and Charecterization of Acclofenac Pregelatinsed Cassava Starch Succinate as a
Microspheres,Asian Journal of pharmaceutics. New Carrier for Drug Delivery, J.Med.Sci.
2008;2(2): 110-115. 2009; 9(6):249-256.
13. Samanta K.M., Tamilvanan S., Babu K., Suresh 25.Fischer S., Foreg C., Merkle P.H., Gander B.,
B., Formulation and Evaluation of Chitosan Coated Plga-Microspheres-A Modular
Chlorpromazine Hydrochloride Loaded Self- System for Targetting Drug Delivery, European
Cross-Linked Gelatin Microcapsules, Indian Cells and Materials. 2004; 7:11-12.

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